Atherosclerosis occurs in millions of individuals in the United States alone and is believed to be responsible for thousands of deaths each year. Diagnosis and monitoring is conventionally performed by radiologic procedures which have the disadvantage of being invasive or semi-invasive procedures. In this proposal we will attempt to develop and immunochemical means of diagnosing and monitoring atherosclerosis. This will be based on a method incorporating blood clearance of radiolabeled antibodies directed against specific constituents of atherosclerotic plaque. For this purpose, we will prepare a panel of monoclonal antibodies against different components of the atherosclerotic plaque. Antibodies against plaque-specific or plaque-associated markers will be selected by comparative immunocytochemical analysis on frozen sections of atherosclerotic and normal arteries from non-human primates and humans. This will enable the identification and selection of antibodies against antigens that are exposed in the lumen of the blood vessel. Monoclonal antibodies against individual plaque antigens will be radiolabeled with 125I and injected into non-human primates for blood clearance studies. In order to control for differences that may exist in the vascular system of different animals, we will utilize a second 131I radiolabeled monoclonal antibody which is known not to bind to antigens in the vascular system. By comparing over time the ratio of these two antibodies in blood, it should be possible to detect specific clearance of the monoclonal antibody that detects antigens within the atherosclerotic plaque. The extent and rate of antibody clearance should be representative of the amount of atherosclerotic plaque in the circulatory system. If successful, this method could be used for early in vivo diagnosis of atherosclerosis and for monitoring the results of therapy in individuals.